NOE AND 2D-NOESY SPECTROSCOPIC STUDIES OF
NAPHTHO[1,2-c]PYRAZOLINE DERIVATIVES
Tariq R. Sobahi
Department of Chemistry, Faculty of Science, King Abdulaziz University,
Jeddah-21589, P.O.Box 80203, Saudi Arabia
‫ مع‬2-arylmethylidene-1-tetralones ‫ بواسطة تكاثف‬naphtho[1,2-c]pyrazoline ‫تم تحضير مشتقات‬
‫ المطروحة لرنين البروتون النووي المغناطيسي و دراسات‬nOe ‫ تم توظيف أطياف‬.‫مشتقات الهيدرازين‬
‫ في مركب‬HN ‫ و‬HM ‫ الطيفية للتمييز بين بروتوني البروكيرال ميثيلين الدياستيريومريين‬2D-NOESY
‫ تقعان تحت‬HM ‫ و‬HJ ‫ وأثبتت أن‬2-methyl-3-phenyl-3,3a,4,5-tetrahydronaphtho[1,2-c]pyrazole
HJ ‫ و‬HH ‫ هذه النتائج أظهرت عالقة متضادة بين البروتونين‬.‫ أعلى المستوى‬HN ‫ و‬HH ‫المستوى و‬
.‫المتجاورين وأكدت على الشكل والترتيب النسبي للمركزين الكيراليين في مشتقات البيرازولين‬
The synthesis of naphtho[1,2-c]pyrazoline derivatives has been achieved via the condensation
of 2-arylmethylidene-1-tetralones with hydrazine derivatives. 1H NMR nOe difference
spectra and 2D-NOESY spectroscopic studies were employed to distinguish between the
diastereotopic prochiral methylene protons HM and HN in 2-methyl-3-phenyl-3,3a,4,5tetrahydronaphtho[1,2-c]pyrazole and proved that HJ and HM are down the plane and HH and
HN are above the plane. These results revealed an anti relationship between the vicinal
protons HH and HJ and confirmed this relative configuration of the two chiral centers in
pyrazoline derivatives.
1
INTRODUCTION
In the last decades the pyrazole derivatives had a considerable interest in the
chemotherapeutic activity. The use of pyrazole derivatives in medicine is undoubtedly the
principal practical application. Certain alkylpyrazoles have shown quite significant
bacteriostatic [1-3], bacteriocidal and fungicidal actions [4-6]. Steroidal compounds whose
structures include pyrazole rings are of interest as possible psychopharmacological agents
[7,8]. Moreover, pyrimidinopyrazoles are being studied in the fight against cancer [9]. On the
other hand, a wide variety of pharmacological properties are encountered with naphthalene
derivatives [10]. Therefore, fused heterocyclic systems incorporating the naphthalene moiety
and pyrazole ring were synthesized by Basaif et al [11] for the purpose of obtaining
compounds of biologically importance.
EXPERIMENTAL
General procedure for preparation of naphtho[1,2-c]pyrazoline derivatives 2-8 [11].
A mixture of the appropriate 2-arylmethylidene-1-tetralone 1 (0.001 mol) and the proper
hydrazine derivative (0.0012 mol) in ethanol (30 ml) was heated under reflux for 3 hrs. Upon
concentration and cooling, the pyrazoline derivative separated out and recrystallized from
ethanol as needles.
Selected
physical
and
spectroscopic
data
for
2-methyl-3-phenyl-3,3a,4,5-
tetrahydronaphtho[1,2-c]pyrazole 2.
mp 136C; FTIR (KBr) max 3065(aromatic CH), 2950-2850(aliphatic CH), 1548(C=N)
cm-1; 1H NMR (400 MHz, CDCl3)  7.94 (1H, dd, J=7.6, 2.3 Hz, Ar HA), 7.48 (2H, d, J=7.3
2
Hz, Ar HB), 7.39 (2H, t, J=7.1 Hz, Ar HC), 7.32 (1H, d, J=7.1 Hz, Ar HD), 7.23 (1H, dd,
J=7.8, 3.6 Hz, Ar HE), 7.21 (1H, dd, J=7.8, 3.4 Hz, Ar HF), 7.14 (1H, dd, J=7.0, 2.1 Hz, Ar
HG), 3.68 (1H, d, J=13.5 Hz, HH), 3.14 (1H, ddd, J=13.5, 13.5, 5.0 Hz, HJ), 2.78 (2H, dd,
J=13.2, 5.0 Hz, HK), 2.82 (1H, s, CH3(L)), 2.17-2.11 (1H, m, HM), 1.88-1.81 (1H, m, HN) ppm;
13
C NMR (100.2 MHz, CDCl3)  152.23 (C=N), 139.63 (Ar quat C), 138.16 (Ar quat C),
129.04 (Ar CH), 128.90 (Ar CH), 128.71 (2Ar CH), 128.3 (Ar quat C), 127.87 (Ar CH),
127.44 (2Ar CH), 126.62 (Ar CH), 124.13 (Ar CH), 80.50 (CHH), 54.68 (CHJ), 42.07
(CH3(L)), 29.28 (CH2(K)), 26.83 (CH2(M+N) ppm; MS (EI) m/z (%) 51 (28), 65 (15), 77 (28), 91
(45), 115 (8), 116 (28), 118 (27), 144 (16), 185 (83), 262 (base, M+); C18H18N2 (262), Calcd.:
C, 82.44; H, 6.87; N, 10.69. Found: C, 82.21; H, 6.56; N, 10.45.
RESULTS AND DISCUSSION
Condensation of 2-arylmethylidene-1-tetralones 1, which prepared via condensation of 1tetralone with aromatic aldehydes in presence of 10% aqueous sodium hydroxide solution,
with hydrazine derivatives in boiling ethanol yielded the corresponding naphtho[1,2c]pyrazoline derivatives 2-8 in good yields [11] (Scheme 1).
An X-ray crystal structure of pyrazoline derivative 2 which obtained by Basaif et al [11]
showed an anti relationship between neighboring protons HH and HJ. Therefore, pyrazoline
derivative 2 was adopted for 1D 1H NMR, nOe and 2D-NOESY spectroscopic studies to
confirm this relative configuration of the two chiral centers in pyrazoline derivatives. The 1H
NMR spectrum of pyrazoline derivative 2 showed a doublet at  3.68 ppm for proton HH with
coupling constant JHH/HJ of 13.5 Hz indicating that vicinal protons HH and HJ are in diaxial
configurations. There is a doublet of doublet of doublet (ddd) at  3.14 ppm for proton HJ,
which couples with the axial proton HH (JHJ/HH =13.5 Hz) to split to two lines which each of
3
them split again to another two lines after coupling with the axial proton HM (JHJ/HM =13.5
Hz) to give four lines. Because of the coupling constant of HJ with HH almost equals the
coupling constant of HJ with HM, the inner two lines coincide to give only three lines, which
each of them split to two lines to give six lines after coupling with the equatorial proton HN
(JHJ/HN =5.0 Hz). There is a doublet of doublet for two equivalent protons HK at  2.78 ppm
which couple with HM (JHK/HM =13.2 Hz) and then couple with HN (JHK/HN =5.0 Hz). There
are two multiplets at  2.17-2.11 and 1.88-1.81 ppm for the axial proton HM and the
equatorial proton HN, respectively.
Attempts to confirm the relationship between the vicinal protons HH and HJ, and to
distinguish between the diastereotopic methylene protons HM and HN in the pyrazoline
derivative 2 were carried out by using nuclear Overhauser effect (nOe) and 2D-NOESY
spectroscopic studies. 1H NMR nOe difference spectra of the pyrazoline derivative 2 are
accumulated in Table 1 and in particular show that irradiation of HA, HB, HF, HJ, methyl L
protons and HN, individually, gave 20.8%, 19.6%, 21.3%, 21.3%, 21.3% and 21.3%
enhancement of signal, respectively, for HM, whereas, all of these irradiations did not give
any enhancement for HN. Irradiation of HE, HH, methylene K protons and HM, individually,
caused 15.4%, 20%, 21.3% and 21.3% enhancement of the signal, respectively, due to HN,
whereas, irradiation of these protons did not affect HM. These results prove that HM is close in
space to HA, HB, HF, HJ, methyl L protons and HN, whilst, HN is close in space to HE, HH,
methylene K protons and HM. All of these results confirm that the diastereotopic prochiral
methylene protons HM and HN are distinguishable.
Irradiation of HM caused 7.9% enhancement of the signal due to HJ, but did not affect HH,
whilst, irradiation of HN gave 7.5% enhancement of signal for HH, but did not affect HJ.
These results prove that HJ and HM are close to each other in space, whereas, HH and HN are
close to each other in space, and hence, one can conclude that HJ and HM are in the same
4
direction which is down of the plane, whilst, HH and HN are in the same direction which is
above the plane.
An X-ray crystal structure for compound 2, which obtained by Basaif et al [11], confirmed
these results that HJ and HM are down of the plane, whereas, HH and HN are above the plane.
Fig. 1 illustrates the 2D-NOESY spectrum of the pyrazoline derivative 2. The onedimensional spectrum is reproduced along one axis of the two-dimensional contour plot.
There are three correlation peaks at  2.15 and 7.48 ppm, 2.15 and 3.14 ppm and 2.15 and
2.82 ppm for HM with HB, HM with HJ and HM with methyl L protons, respectively. This
proves that HM is in close position to HB, HJ and methyl L protons. There are two correlation
peaks at  1.85 and 3.68 ppm and 1.85 and 2.87 ppm for HN with HH and HN with methylene
K protons, respectively and this proves that HN is close in space to HH and methylene K
protons. These results confirm that the diastereotopic prochiral methylene protons HM and HN
are distinguishable.
There are two correlation peaks at  2.15 and 3.14 ppm and 1.85 and 3.68 ppm for HM with
HJ and HN with HH, respectively, proving that HM is in close position to HJ and HN is in close
position to HH. These results confirm the previous result that HM and HJ are in the same
direction which is down of the plane, whereas, HN and HH are in the same direction i.e. above
the plane.
By conclusion, all of these results determined by 2D-NOESY spectrum confirm all results
determined by nOe difference spectra.
All the signals of the pyrazoline derivatives 2 were assigned by nOe and 2D-NOESY
spectroscopic studies.
5
O
N
+
RNHNH2
ethanol, reflux
X
R
N H
H
X
1
2 X=H, R=CH3
3 X=p-CH3, R=CH3
4 X=H, R=C6H5 5 X=p-CH3, R=C6H5
6 X=H, R=p-ClC6H4
7 X=p-CH3, R=p-ClC6H4
8 X=p-CH3, R=p-NH2SO2C6H4
Scheme 1
6
MeL
HA
N
N
HH HB
HE
HC
HJ
HM
HF
HG
HK H H N H B
K
HD
HC
2
Table 1. 1H NMR steady state nOe data for the naphtho[1,2-c]pyrazoline derivative 2.
Irradiation
Signal enhancement (%)
Site
HA
HB
HC
HD
HE
HF
HG
HH
HJ
HK
HL
HM
HN
HA
-
-
-
-
3.8
14.6
-
4.6
12.5
-
-
20.8
-
HB
-
-
7.1
-
2.9
5.8
12.5
10
20
-
-
19.6
-
HC
-
-
-
-
-
-
-
20.8
-
-
-
-
-
HD
-
-
-
-
-
-
-
16.3
21.3
-
-
-
-
HE
16.7
-
-
-
-
-
11.3
6.3
21.3
-
-
-
15.4
HF
11.7
-
-
-
-
-
-
8.3
-
-
-
21.3
-
HG
-
-
-
-
-
-
-
6.7
13.3 16.7
-
-
-
HH
-
13.8
-
-
-
-
-
-
8.3
-
-
-
20
HJ
-
4.2
-
-
-
-
6.7
6.3
-
-
-
21.3
-
HK
-
-
-
-
-
-
12.1
2.5
13.8
-
-
-
21.3
HL
-
-
-
-
-
-
-
20.4
-
-
-
21.3
-
HM
-
-
-
-
-
-
-
-
7.9
-
-
-
21.3
HN
-
-
-
-
-
-
-
7.2
-
7.1
-
21.3
-
7
FIG 1. The 2D-NOESY 400 MHz NMR spectrum of the naphtho[1,2-c]pyrazoline
derivative 2.
8
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